| 1 | Schizophr. Res. 2010 Jul 120: 131-42 |
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| PMID | 20347268 |
| Title | Convergent evidence shows a positive association of interleukin-1 gene complex locus with susceptibility to schizophrenia in the Caucasian population. |
| Abstract | Recent genetic studies have revealed that the Interleukin-1 (IL1) gene complex (IL1 alpha, IL1 beta and IL1 receptor antagonist) is associated with schizophrenia, but contradictory findings have also been reported. We investigated the association of the IL1 gene complex locus and schizophrenia using meta-analytic techniques, covering all published data up to January 2010, to restrict to the most commonly reported 4 single nucleotide polymorphisms (SNP). We also explored potential sources of heterogeneity and to investigate whether ancestry and study design moderated any association. The combined allele-wise odds ratio (OR) for schizophrenia of the rs16944 (IL1B gene; T-511C) polymorphism was 0.86 (95% CI: 0.77to 0.96).When applying stratified analysis to this polymorphism, the pooled allele-wise OR was 0.88 (95% CI, 0.79 to 0.97) in 10 population-based studies and 0.85 (95% CI: 0.73 to 0.99) in Caucasian samples. In a stratified analysis of the rs1143634 (IL1B gene; T3953C) polymorphism, the pooled genotype-wise results in a dominant model were also statistically significant both in a population-based study subgroup with summary OR of 0.64 (95% CI: 0.41 to 0.99) and a Caucasian population subgroup with summary OR of 0.62 (95% CI: 0.40 to 0.97). Neither combined nor stratified analyses found any association of the rs1800587 (IL1A gene; T-889C) or rs1794068 (IL1RA Gene; IL1RN_86 bp; T/C) with schizophrenia susceptibility. Our study suggests the IL1B gene or the IL1 gene complex may play a moderate role in the etiology of schizophrenia in the Caucasian population. |
| SCZ Keywords | schizophrenia |
| 2 | Neuropsychopharmacology 2011 Feb 36: 616-26 |
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| PMID | 21107309 |
| Title | Genome-wide pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia. |
| Abstract | Neurocognitive deficits are a core feature of schizophrenia and, therefore, represent potentially critical outcome variables for assessing antipsychotic treatment response. We performed genome-wide association studies (GWAS) with 492K single nucleotide polymorphisms (SNPs) in a sample of 738 patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness study. Outcome variables consisted of a neurocognitive battery administered at multiple time points over an 18-month period, measuring processing speed, verbal memory, vigilance, reasoning, and working memory domains. Genetic mediation of improvements in each of these five domains plus a composite neurocognitive measure was assessed for each of five antipsychotics (olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone). Six SNPs achieved genome-wide significance using a pre-specified threshold that ensures, on average, only 1 in 10 findings is a false discovery. These six SNPs were located within, or in close proximity to, genes EHF, SLC26A9, DRD2, GPR137B, CHST8, and IL1A. The more robust findings, that is those significant across multiple neurocognitive domains and having adjacent SNPs showing evidence for association, were rs286913 at the EHF gene (p-value 6.99 × 10(-8), q-value 0.034, mediating the effects of ziprasidone on vigilance), rs11240594 at SLC26A9 (p-value 1.4 × 10(-7), q-value 0.068, mediating the effects of olanzapine on processing speed), and rs11677416 at IL1A (p-value 6.67 × 10(-7), q-value 0.081, mediating the effects of olanzapine on working memory). This study has generated several novel candidate genes for antipsychotic response. However, our findings will require replication and functional validation. To facilitate replication efforts, we provide all GWAS p-values for download. |
| SCZ Keywords | schizophrenia |
| 3 | Schizophr. Res. 2015 Dec 169: 1-9 |
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| PMID | 26481614 |
| Title | Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population. |
| Abstract | schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed. |
| SCZ Keywords | schizophrenia |
| 4 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2016 Mar 171: 181-202 |
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| PMID | 26462458 |
| Title | Currently recognized genes for schizophrenia: High-resolution chromosome ideogram representation. |
| Abstract | A large body of genetic data from schizophrenia-related research has identified an assortment of genes and disturbed pathways supporting involvement of complex genetic components for schizophrenia spectrum and other psychotic disorders. Advances in genetic technology and expanding studies with searchable genomic databases have led to multiple published reports, allowing us to compile a master list of known, clinically relevant, or susceptibility genes contributing to schizophrenia. We searched key words related to schizophrenia and genetics from peer-reviewed medical literature sources, authoritative public access psychiatric websites and genomic databases dedicated to gene discovery and characterization of schizophrenia. Our list of 560 genes were arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms. Genome wide pathway analysis using GeneAnalytics was carried out on the resulting list of genes to assess the underlying genetic architecture for schizophrenia. Recognized genes of clinical relevance, susceptibility or causation impact a broad range of biological pathways and mechanisms including ion channels (e.g., CACNA1B, CACNA1C, CACNA1H), metabolism (e.g., CYP1A2, CYP2C19, CYP2D6), multiple targets of neurotransmitter pathways impacting dopamine, GABA, glutamate, and serotonin function, brain development (e.g., NRG1, RELN), signaling peptides (e.g., PIK3CA, PIK4CA) and immune function (e.g., HLA-DRB1, HLA-DQA1) and interleukins (e.g., IL1A, IL10, IL6). This summary will enable clinical and laboratory geneticists, genetic counselors, and other clinicians to access convenient pictorial images of the distribution and location of contributing genes to inform diagnosis and gene-based treatment as well as provide risk estimates for genetic counseling of families with affected relatives. © 2015 Wiley Periodicals, Inc. |
| SCZ Keywords | schizophrenia |